Radiation Safety and External Radiation Exposure Rate of Patients Receiving I-131 Therapy for Hyperthyroidism and Remnant Ablation as Outpatient: An Institutional Experience.

Objective Our objective was to study the radiation exposure rate as function of time in the administration of radioiodine iodine-131 (I-131) for the treatment of thyrotoxicosis or Graves' disease and remnant ablation on an outpatient basis at the Department of Nuclear Medicine, and also, to study the impact of revised discharge criteria for radioiodine therapy enforced by the Atomic Energy Regulatory Board (AERB) of India. Materials and Methods This study included patients who underwent low-dose radioiodine therapy using I-131. Patients were classified into two different groups, that is, group A and group B. Group A included patients receiving low dose I-131 for the treatment of thyrotoxicosis, whereas group B included patients receiving I-131 therapy for the ablation of residual thyroid tissue after total thyroidectomy. The radiation exposure rate was measured using a radiation detector in milli roentgen per hour (mR/h) at 5 cm distance of stomach and neck levels and with the patient standing at the distance of 1 m after oral administration of I-131 at 0, 1, and 2 hours. Results A total of 134 (17 males and 117 females) patients were included in the study. Group A comprised 102 (14 male and 88 females) patients and group B of 32 (3 males and 29 females) patients. At the neck level, the average exposure rate in group A versus group B after 0, 1, and 2 hours was observed to be 6.9 versus 22.27 mR/h, 33.67 versus 43.39 mR/h, and 41.75 versus 48.90 mR/h, respectively. At the stomach level, the exposure rate was 23.65 versus 71.32 mR/h, 13.27 versus 48.45 mR/h, and 9.91 versus 39.43 mR/h after 0, 1, and 2 hours, respectively. At a distance of 1 m, the exposure rate was 1.31 versus 2.99 mR/h, 1.05 versus 2.58 mR/h, and 0.92 versus 2.21 mR/h, respectively. Conclusion Exposure rate measured for patients treated with up to 1,110 MBq (30 mCi) of I-131 was under permissible limits as per revised discharged limits, that is, 50 µSv/h (5 mR/h) prescribed by AERB, India. The patients undergoing radioiodine therapy I-131 (up to 1,110 MBq/30 mCi) can be discharged safely 2 hours postadministration following good work practice along with providing proper radiation safety instructions to patients.

Screening of wild species and transcriptome profiling to identify differentially regulated genes in response to late blight resistance in potato.

Late blight (Phytophthora infestans) is a serious disease of potatoes. The aim of this study was to screen wild potato species and identify differentially expressed genes (DEGs) associated with late blight resistance. Wild potato species such as PIN45 (Solanum pinnatisectum), CPH62 (Solanum cardiophyllum), JAM07 (Solanum jamesii), MCD24 (Solanum microdontum), PLD47 (Solanum polyadenium), and cv. Kufri Bahar (control) were tested by artificial inoculation of P. infestans under controlled conditions. Transcriptomes of the leaf tissues (96 h post-inoculation) were sequenced using the Illumina platform. Statistically significant (p < 0.05) DEGs were analyzed in wild species by comparison with the control, and upregulated (>2 log2 fold change, FC) and downregulated (<-2 log2 FC) genes were identified. DEGs were functionally characterized with Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Selected genes were validated by real-time PCR analysis to confirm RNA-seq results. We identified some upregulated genes associated with late blight resistance in wild species such as cytochrome P450, proline-rich protein, MYB transcription factor MYB139, ankyrin repeat-containing protein, and LRR receptor-like serine/threonine-protein kinase in PIN45; glucosyltransferase, fructose-bisphosphate aldolase, and phytophthora-inhibited protease 1 in CPH62; steroid binding protein and cysteine proteinase 3 in JAM07; glycine-rich cell wall structural protein 1 and RING finger protein in MCD24; and cysteine proteinase 3 and major latex protein in PLD47. On the other hand, downregulated genes in these species were snakin-2 and WRKY transcription factor 3 in PIN45; lichenase and phenylalanine ammonia-lyase 1 in CPH62; metallothionein and LRR receptor-like serine/threonine-protein kinase in JAM07; UDP-glucoronosyl/UDP-glucosyl transferase family protein and steroid binding protein in MCD24; and cytoplasmic small heat shock protein class I and phosphatase PLD47. Our study identified highly resistant wild potato species and underlying genes such as disease resistance, stress response, phytohormones, and transcription factors (e.g., MYB, WRKY, AP2/ERF, and AN1) associated with late blight resistance in wild potato species.

Evaluation of Tetrofosmin Cold Kit Fractionation Using Alternative New Method of Quality Control for Testing Radiochemical Purity.

Objective The aim of this study is to establish a method for the fractionation of tetrofosmin cold kit under different storage conditions and to optimize an alternate chromatography method from the reference method to test radiochemical purity (RCP). Materials and Methods Tetrofosmin cold kit vial was fractionated aseptically in six equal fractions and stored in vials and syringes. To test the stability of the reconstituted solution for a longer duration, the mother vials and syringes were stored at two different temperatures, that is, at 4°C and at -20°C till further used. Radiolabeling of fractionated tetrofosmin was performed as per the standard labeling protocol. Radionuclide purity, radioassay, and pH were tested. Radiolabeling efficiency and RCP were determined by paper chromatography. Results Radionuclide purity of eluate was greater than 99.9%. The pH of technetium-99m (Tc-99m) eluate and Tc-99m tetrofosmin was between 4.5-7.5 and 7.5-9.5, respectively. The deviation in the radioactivity during all measurements was less than 1%. The kits fractioned in glass vials resulted in higher radiolabeling yield and RCP as compared with kits fractionated in syringes. The RCP of glass vial versus syringe was observed to be greater than 95 versus 90% and 95 versus 80% at -20°C and 4°C, respectively. Conclusion Tetrofosmin kit can be used in a cost-effective manner by fractionation. One tetrofosmin vial can be used in six fractions for up to 15 days when stored at -20°C and 4°C freezer temperature. The alternative method to check the RCP of Tc-99m tetrofosmin is safer and less time consuming as compared with the reference method.

Root system architecture for abiotic stress tolerance in potato: Lessons from plants.

The root is an important plant organ, which uptakes nutrients and water from the soil, and provides anchorage for the plant. Abiotic stresses like heat, drought, nutrients, salinity, and cold are the major problems of potato cultivation. Substantial research advances have been achieved in cereals and model plants on root system architecture (RSA), and so root ideotype (e.g., maize) have been developed for efficient nutrient capture to enhance nutrient use efficiency along with genes regulating root architecture in plants. However, limited work is available on potatoes, with a few illustrations on root morphology in drought and nitrogen stress. The role of root architecture in potatoes has been investigated to some extent under heat, drought, and nitrogen stresses. Hence, this mini-review aims to update knowledge and prospects of strengthening RSA research by applying multi-disciplinary physiological, biochemical, and molecular approaches to abiotic stress tolerance to potatoes with lessons learned from model plants, cereals, and other plants.

Germplasm, Breeding, and Genomics in Potato Improvement of Biotic and Abiotic Stresses Tolerance.

Potato is one of the most important food crops in the world. Late blight, viruses, soil and tuber-borne diseases, insect-pests mainly aphids, whiteflies, and potato tuber moths are the major biotic stresses affecting potato production. Potato is an irrigated and highly fertilizer-responsive crop, and therefore, heat, drought, and nutrient stresses are the key abiotic stresses. The genus Solanum is a reservoir of genetic diversity, however, a little fraction of total diversity has been utilized in potato breeding. The conventional breeding has contributed significantly to the development of potato varieties. In recent years, a tremendous progress has been achieved in the sequencing technologies from short-reads to long-reads sequence data, genomes of Solanum species (i.e., pan-genomics), bioinformatics and multi-omics platforms such as genomics, transcriptomics, proteomics, metabolomics, ionomics, and phenomics. As such, genome editing has been extensively explored as a next-generation breeding tool. With the available high-throughput genotyping facilities and tetraploid allele calling softwares, genomic selection would be a reality in potato in the near future. This mini-review covers an update on germplasm, breeding, and genomics in potato improvement for biotic and abiotic stress tolerance.

Resistance Evaluation for Native Potato Accessions against Late Blight Disease and Potato Cyst Nematodes by Molecular Markers and Phenotypic Screening in India.

The potato originated in southern Peru and north-western Bolivia (South America). However, native accessions have also been cultivated in India for many years. Late blight, caused by the fungus Phytophthora infestans, is the most devastating potato disease, while potato cyst nematode (Globodera spp.) (PCN) is another economically significant quarantine-requiring pest in India. In this study, we have generated a new Indian native collection of 94 potato accessions collected from different parts India. These accessions were screened against late blight and potato cyst nematode resistance by using gene-based molecular markers and phenotypic screening methods. Marker assisted selection using R1 gene-specific marker CosA210 revealed a late blight resistance gene in 11 accessions. PCN resistance bands were found in 3 accessions with marker TG689141, 5 accessions with marker 57R452, and 1 accession having Gro1-4-1602 marker for G. rostochiensis (Ro1,4), while 64 accessions amplified marker HC276 indicating G. pallida (Pa2,3) resistance gene (GpaVvrn QTL). On the other hand, phenotypic screening against late blight resistance under natural epiphytic conditions (hot-spot) revealed three accessions with high resistance, while others were resistant (1 accession), moderately resistant (5 accessions), susceptible (29 accessions), and highly susceptible (56 accessions). For G. rostochiensis (golden cyst nematode) and G. pallida (white cyst nematode) resistance, accessions were grouped into highly resistant (3, 3), resistant (0, 2), moderately resistant (6, 29), susceptible (32, 30), and highly susceptible (53, 30), respectively, for the two PCN species. Collectively, we identified promising accessions with high resistance to late blight (JG-1, Kanpuria Safed, and Rangpuria), and also highly resistant to both Globodera species (Garlentic, Jeevan Jyoti, and JG-1). Our findings suggested that these accessions would be useful for late blight and PCN resistance breeding, as well as future molecular studies in potatoes.

Efficacy of dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin scintigraphy for the assessment of thyroid nodules.

INTRODUCTION: Radioisotope methods have shown to be useful in the non-invasive diagnosis of thyroid nodules over the past years. The present prospective study aims to evaluate the efficacy of gamma imaging using single and dual tracer using Tc-99m pertechnetate and Tc-99m tetrofosmin for evaluation and management of thyroid nodules. METHODS: Dynamic (perfusion) imaging was performed after injecting 148-185 MBq (4-5 mCi) of Tc-99m pertechnetate followed by static imaging. A second, dynamic (perfusion) imaging study within same week was performed with 296-370MBq (8-10mCi) of Tc-99m tetrofosmin on same group of patients followed by early and delayed images. Results of radionuclide perfusion scan from both studies were compared qualitatively with postsurgical histopathology or fine needle aspiration cytology (FNAC). RESULTS: Total 65 nodules in 50 patients were included in the study. With single tracer, the specificity and accuracy of Tc-99m pertechnetate was 23% and 45% and for Tc-99m tetrofosmin scan was 40% and 49%. When dual tracers were evaluated for the same group of patients, the specificity was 56% and accuracy was 55%. CONCLUSION: Dual Tracer technique with Tc-99m pertechnetate and Tc-99m tetrofosmin could be helpful in selecting nodules need surgical intervention. This technique can be used for convenient and rapid diagnostic evaluation of thyroid nodules non-invasively. We suggest a combination of fine needle aspiration biopsy and dual use of Tc-99m-pertechnetate and Tc-99m-tetrofosmin as a routine diagnostic approach to thyroid nodules.

Lycopene modulates cellular proliferation, glycolysis and hepatic ultrastructure during hepatocellular carcinoma.

AIM: To investigate the effect of lycopene extracted from tomatoes (LycT) on ultrastructure, glycolytic enzymes, cell proliferation markers and hypoxia during N-Nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. METHODS: Female BALB/c mice were randomly divided into four groups: The Control, NDEA (200 mg NDEA/kg b.w. given i.p.), LycT (5 mg/kg b.w. given orally on alternate days) and LycT + NDEA group. The mRNA and protein expression of various cell proliferation markers (PCNA, Cyclin D1, and p21) were assessed by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. The ultrastructure of hepatic tissue was analyzed using scanning and transmission electron microscopy. The enzymatic activity of glycolytic enzymes was estimated using standardized protocols, while glucose-6-phosphate dehydrogenase activity level was estimated using a kit obtained from Reckon Diagnostic P. Ltd. (India). RESULTS: Uncontrolled proliferation in the liver of NDEA (P ≤ 0.001) mice was evident from the high expression of cell-proliferation associated genes (PCNA, Cyclin D1, and p21) when compared to control and LycT mice. In addition, enhanced activities of hexokinase, phosphoglucoisomerase, aldolase, glucose-6-phosphate dehydrogenase and hypoxia-inducible factor-1α were observed in NDEA mice as compared to control (P ≤ 0.001) and LycT (P ≤ 0.001) mice. The alterations in hepatic ultrastructure observed in the NDEA group correlated with the changes in the above parameters. LycT pre-treatment in NDEA-challenged mice ameliorated the investigated pathways disrupted by NDEA treatment. Moreover, hepatic electron micrographs from the LycT + NDEA group showed increased macrophages, apoptotic bodies and well-differentiated hepatocellular carcinoma (HCC) in comparison to undifferentiated HCC as observed in the NDEA treated group. CONCLUSION: This study demonstrates that dietary supplementation with LycT has a multidimensional role in preventing HCC development.

Neurologic Complications in Treated HIV-1 Infection.

Effective combination antiretroviral therapy has transformed HIV infection into a chronic disease, with HIV-infected individuals living longer and reaching older age. Neurological disease remains common in treated HIV, however, due in part to ongoing inflammation and immune activation that persist in chronic infection. In this review, we highlight recent developments in our understanding of several clinically relevant neurologic complications that can occur in HIV infection despite treatment, including HIV-associated neurocognitive disorders, symptomatic CSF escape, cerebrovascular disease, and peripheral neuropathy.

Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma.

Targeting altered pathways during initial stage of hepatocellular carcinoma (HCC) development is viewed as an effective and promising strategy to control this disease. Present study investigated the potential effect of lycopene-enriched tomato extract (LycT) on hypoxia-induced factor (HIF)-1α, HOX, VEGF, CD31, matrix metalloproteinase (MMP)-2, MMP-9, and alpha fetoprotein (AFP)expression during initial stages of N-nitrosodiethylamine (NDEA) induced HCC. Female Balb/c mice (8-10 wk) were assigned to 4 groups: control, NDEA (200 mg NDEA i.p./kg body weight, cumulative), LycT (5 mg lycopene orally/kg body weight; 3 times a week), and LycT + NDEA. LycT treatment began 2 wk before NDEA administration and continued until the end of the 10 wk study. The onset of HCC by NDEA was associated with significant alteration in serum biochemical markers [alanine transaminases (ALT), aspartate transaminases (AST), and alkaline phosphatases (ALP), lactate dehydrogenase (LDH), urea, A/G ratio, and bilirubin] and in liver histopathology. LycT treatment significantly reduced the levels of these markers. LycT treatment to NDEA mice also led to significant reduction in protein levels of AFP, HIF-1α, VEGF, CD31, MMP-2, and MMP-9 in comparison with NDEA group alone. These parameters are important biomarkers of hypoxia, angiogenesis, and metastasis, which reflect the advanced disease stage. The study provides evidence that prophylactic dietary supplementation with LycT may counteract HCC progression and/or protect against disease onset.

Identification of Streptococcus intermedius central nervous system infection by use of PCR and electrospray ionization mass spectrometry.

We describe the utility of PCR and electrospray ionization with mass spectrometry (PCR/ESI-MS) of culture-negative cerebrospinal fluid (CSF) in order to identify Gram-positive cocci noted on a Gram stain of CSF from a previously healthy 26-year-old man with community-acquired pneumonia (CAP) and multiple brain abscesses. CSF samples were obtained 2 weeks apart, first by lumbar puncture and 2 weeks later from an external ventricular drain that was inserted into the right ventricle. Both CSF cultures were negative. A Gram stain of bronchoalveolar lavage (BAL) fluid was notable for many Gram-positive cocci (GPC), but cultures of BAL fluid and subcarinal lymph node biopsy tissue were negative. PCR/ESI-MS detected Streptococcus intermedius, a common cause of brain abscesses, in both CSF samples as well as in the fixed tissue from the biopsy. This unique case confirms S. intermedius pulmonary infection as the source of metastatic CNS infection and reveals the potential of PCR/ESI-MS to detect a streptococcal pathogen not captured by conventional cultures.

Rapid identification of Aspergillus terreus from bronchoalveolar lavage fluid by PCR and electrospray ionization with mass spectrometry.

We describe the application of PCR and electrospray-ionization with mass spectrometry (PCR/ESI-MS) to culture-negative bronchoalveolar lavage (BAL) fluid in order to identify septate hyphae noted by Gomori methenamine silver (GMS) staining of the fluid that was obtained from an immunocompromised woman with neutropenia following induction chemotherapy for treatment of acute myelogenous leukemia (AML). The patient was treated with empirical antifungal therapy, including intrathecal amphotericin B, while results of fungal cultures were pending. Ultimately, Aspergillus terreus, an amphotericin-resistant mold, was cultured from bilateral brain abscesses. PCR/ESI-MS correctly identified the mold.

Isolated noncompaction of the left ventricular myocardium in adults: a systematic overview.

BACKGROUND: Owing to inconsistent diagnostic criteria and small heterogeneous cohorts, little is known about the long-term outcomes of adult left ventricular noncompaction (LVNC), a rare cardiomyopathy with potentially serious outcomes. This systematic overview aimed to better delineate the natural history of adult LVNC. METHOD AND RESULTS: A comprehensive computerized search using "noncompaction" and its synonyms initially identified 206 articles, with reference lists subsequently hand scanned. These searches yielded 5 studies that were eligible for this systematic overview, identifying adult cohorts with isolated LVNC diagnosed by similar echocardiographic criteria. This combined cohort (n = 241) was followed for a mean duration of 39 months. The annualized event rate was 4% for cardiovascular deaths, 6.2% for cardiovascular death and its surrogates (heart transplantation and appropriate implantable cardioverter-defibrillator shocks), and 8.6% for all cardiovascular events (death, stroke, implantable cardioverter-defibrillator shocks, and heart transplantation.) Familial occurrence of LVNC in first-degree relatives was identified by echocardiography in 30% of index cases who were screened. CONCLUSION: LVNC is an increasingly recognized cardiomyopathy diagnosed by echocardiography and is associated with familial tendencies, arrhythmias, thromboembolism, advanced heart failure, and death.

Non-uniform recovery of left ventricular transmural mechanics in ST-segment elevation myocardial infarction.

BACKGROUND: After a transient ischemic episode, the subendocardial region is more severely injured than outer subepicardial layers and may regain a proportionately greater degree of mechanical function in the longitudinal direction. We sought to explore left ventricular (LV) transmural mechanics in patients with ST-segment elevation myocardial infarction (STEMI) for determining the mechanism underlying recovery of global LV function after primary percutaneous coronary intervention (PCI). METHODS: A total of 42 patients (62 +/- 11 years old, 71% male) with a first STEMI underwent serial assessments of LV longitudinal, circumferential and radial strains (LS, CS and RS) by selective tracking of subendocardial and subepicardial regions within 48 hours and a median of 5 months after PCI. LV mechanical parameters were compared with sixteen age and gender matched normal controls. RESULTS: In comparison with controls, endocardial and epicardial LS were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and was associated with improvement in endocardial and epicardial LS (P < 0.001 and P = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall motion score index, however, remained persistently abnormal. The change in endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated with the improvement in LVEF, independent of the location of STEMI and the presence of underlying multivessel disease. CONCLUSIONS: In patients with STEMI treated by PCI, the recovery of LV subendocardial shortening strain seen in the longitudinal direction underlies the improvement in LV global function despite persistent abnormalities in radial mechanics and wall motion score index.

Atrial fibrillation ablation in cor triatriatum: value of intracardiac echocardiography.

A 72-year old male, referred for percutaneous atrial fibrillation ablation, was found to have cor triatriatum during routine, pre-procedural transesophageal echocardiography. Accessing the superior pulmonary venous atrium and wide area circumferential ablation was guided by intracardiac echocardiography and performed without complications. The patient remains symptom-free, off anti-arrhythmic drug therapy, for 6 months following ablation. In this report, we emphasize the value of using intracardiac echocardiography during catheter ablation in patients with cor triatriatum.

Reducing Ionizing Radiation Associated with Atrial Fibrillation Ablation: An Ultrasound-Guided Approach.

Radiation exposure with cardiac interventional procedures is an emerging concern. Patients receiving radiofrequency ablation for atrial fibrillation (AF) still routinely undergo pre-ablation computed tomography (CT) scans for definition of left atrial and pulmonary vein anatomy, as well as creation of a surrogate geometry. In an effort to decrease ionizing radiation associated with AF ablation, an ultrasound-guided surrogate geometry approach is proposed as an alternative to routine CT imaging. Ten patients underwent AF ablation using intracardiac ultrasound for the creation of a surrogate left atrial geometry (CartoSound, Biosense Webster, CA); and ten control-cases who had conventional CT-guided imaging (CartoMerge, Biosense Webster, CA) were matched for age, gender, and type of catheter ablation. Sources of radiation included 1) intraprocedural fluoroscopy (CartoSound: 151 ± 43 mGray*cm^2, CartoMerge: 174 ± 130 mGray*cm^2; p=0.6) and 2) CT ionizing radiation (CartoSound: 0 mSv, CartoMerge 9.4 ± 2.3 mSv/CT scan.) When comparing clinical success rates after a trial of previously ineffective anti-arrhythmic drugs, ultrasound-guided AF ablation was non-inferior to a CT-guided approach. This potentially obviates the need for CT-guided imaging, therefore reducing doses of ionizing radiation by nearly 10 mSv per AF catheter ablation.

Myasthenia gravis: a study from India.

BACKGROUND: We present the findings from the largest hospital-based studies on myasthenia gravis from India, using data collected over a period of 43 years from the Neurology Department in a tertiary referral center in India. OBJECTIVES: To study the clinical presentation, age at onset, gender distribution, serological status and thymic pathology in patients with myasthenia gravis. MATERIALS AND METHODS: A retrospective study was carried out using records of patients with myasthenia gravis from the years 1965 to 2008. RESULTS: Of 841 patients, 836 (611 males and 225 females) had acquired myasthenia (myasthenia gravis) and five congenital myasthenia. The median age at onset was 48 years (males 53 years and females 34 years). The peak age at onset for males was in the sixth and seventh decade and in females, in the third decade. Two hundred and twenty-two (26.31%) patients had ocular and 616 (73.68%) generalized myasthenia. Serological studies were done in 281 patients with myasthenia gravis for Acetylcholine receptor (AchR) antibodies of which 238 (84.70%) were seropositive. The most common histopathology was thymoma and the second most common was thymic hyperplasia. CONCLUSION: Myasthenia gravis in our study was more common in males (M:F of 2.70:1). There was a single peak of age at onset (males sixth to seventh decade; females third decade). The higher prevalence of thymomas in this series is in all probability related to selection bias as patients with thymic enlargement or more severe disease underwent thymectomy. Thymoma was more common in males; hyperplasia in females.

Esophageal perforation as a complication of esophagogastroduodenoscopy.

Fifty years ago, esophageal perforation was common after rigid upper endoscopy. The arrival of flexible endoscopic instruments and refinement in technique have decreased its incidence; however, esophageal perforation remains an important cause of morbidity and mortality. This complication merits a high index of clinical suspicion to prevent sequelae of mediastinitis and fulminant sepsis. Although the risk of perforation with esophagogastroduodenoscopy alone is only 0.03%, this risk can increase to 17% with therapeutic interventions in the setting of underlying esophageal and systemic diseases. A wide spectrum of management options exist, ranging from conservative treatment to surgical intervention. Prompt recognition and management, within 24 hours of perforation, is critical for favorable outcomes.